Announcement • Jul 15
Acumen Pharmaceuticals Presents Enhanced Brain Delivery Program Data and Early Alzheimer’S Disease Insights At Alzheimer’S Association International Conference 2026
Acumen Pharmaceuticals announced new findings presented at the Alzheimer's Association International Conference 2026 in London. Following collaboration with JCR Pharmaceuticals Co., Ltd. (JCR) on EBD candidate development, studies demonstrated improved brain penetration of anti-AßO antibodies through transferrin receptor-mediated delivery across both mouse and non-human primate models. Additionally, research from early symptomatic AD patients highlighted the lived experience among ALTITUDE-AD trial participants and their study partners. EBD bispecific antibodies targeting both AßOs and hTfR showed improved brain penetration compared to the native anti-AßO antibodies, which may enable administration with a low-volume delivery device and reduce the delivered dose required for efficacy. EBD candidate ACU401 achieves up to 40-fold greater frontal cortex exposure in non-human primates and significant increase in exposures in deep brain regions. No hematological safety signals observed in non-human primates, demonstrating low potential for anemia. To evaluate transferrin receptor (TfR)-mediated brain delivery, Acumen and JCR developed and characterized anti-AßO antibody fusion proteins incorporating J-Brain Cargo, JCR’s clinically validated platform targeting the TfR, to facilitate brain uptake in humanized TfR mice. Fusion with anti-TfR fragments did not alter AßO affinity or selectivity. All EBD constructs achieved substantially higher brain levels than native anti-AßO antibodies, with each construct displaying a unique pharmacokinetic profile. Systemic absorption was confirmed after subcutaneous dosing and constructs retained the ability to bind Aß species of interest in human AD brain tissue. In collaboration with JCR, Acumen evaluated three bispecific antibodies fusing anti-AßO antibody (ACU234) with anti-TfR antibody fragments in cynomolgus monkeys. After intravenous dosing, all three bispecific antibodies achieved greater brain exposure than ACU234 alone, with at least 14-fold higher levels in the frontal cortex. Candidate molecule ACU401 demonstrated particularly robust brain penetration: 22-fold higher at 3 hours and 40-fold higher at 24 hours in the frontal cortex, with similar trends observed in the hippocampus and putamen. No hematological findings suggestive of anemia were observed. These results, together with evidence of systemic absorption after subcutaneous dosing, highlight the potential of EBD molecules for further development in early AD. Semi-structured interviews were conducted with 38 participants and their study partners prior to treatment in the ALTITUDE-AD Phase 2 study. Participants described pervasive memory-related challenges including forgetfulness, difficulty completing tasks, and communication difficulties. Emotional impacts, frustration, worry, and reduced confidence contributed to social withdrawal and reduced activity participation. Participants also reported actively managing others’ perceptions of their symptoms through masking and selective disclosure. Together, results illustrate the diverse ways individuals with early Alzheimer's disease experience, respond to, and cope with cognitive and functional changes, underscoring the importance of capturing patient experience directly to better understand meaningful benefit at this stage of disease. Sabirnetug (ACU193) is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble amyloid beta oligomers (AßOs), which are a highly toxic and pathogenic form of Aß, relative to Aß monomers and amyloid plaques. Soluble AßOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function and induce neurodegeneration. By selectively targeting toxic soluble AßOs, sabirnetug aims to address the hypothesis that soluble AßOs are an early and persistent underlying cause of the neurodegenerative process in Alzheimer’s disease. Sabirnetug has been granted Fast Track designation for the treatment of early AD by the U.S. Food and Drug Administration and is currently being evaluated in a Phase 2 study in patients with early AD. Initiated in 2024, ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sabirnetug (ACU193) infusions administered once every four weeks in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease. The study has enrolled 542 individuals with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to AD) at multiple investigative sites located in the United States, Canada, the European Union and the United Kingdom. Topline results are expected in late 2026.
